Imipramine Is an Orally Active Drug against Both Antimony Sensitive and Resistant Leishmania donovani Clinical Isolates in Experimental Infection

Background: In an endeavor to find an orally active and affordable antileishmanial drug, we tested the efficacy of a cationic amphiphilic drug, imipramine, commonly used for the treatment of depression in humans. The only available orally active antileishmanial drug is miltefosine with long half life and teratogenic potential limits patient compliance. Thus there is a genuine need for an orally active antileishmanial drug. Previously it was shown that imipramine, a tricyclic antidepressant alters the protonmotive force in promastigotes, but its in vivo efficacy was not reported. Methodology/Principal Findings: Here we show that the drug is highly active against antimony sensitive and resistant Leishmania donovani in both promastigotes and intracellular amastigotes and in LD infected hamster model. The drug wasfound to decrease the mitochondrial transmembrane potential of Leishmania donovani (LD) promastigotes and purified amastigotes after 8 h of treatment, whereas miltefosine effected only a marginal change even after 24 h. The drug restores defective antigen presenting ability of the parasitized macrophages. The status of the host protective factors TNF a, IFN c and iNOS activity increased with the concomitant decrease in IL 10 and TGF b level in imipramine treated infected hamsters and evolution of matured sterile hepatic granuloma. The 10-day therapeutic window as a monotherapy, showing about 90% clearance of organ parasites in infected hamsters regardless of their SSG sensitivity. Conclusions: This study showed that imipramine possibly qualifies for a new use of an old drug and can be used as an effective orally active drug for the treatment of Kala-azar

The stigma of low opioid prescription in the hospitalized multimorbid elderly in Italy

The primary aim of this study was to evaluate the prevalence of opioid prescriptions in hospitalized geriatric patients. Other aims were to evaluate factors associated with opioid prescription, and whether or not there was consistency between the presence of pain and prescription. Opioid prescriptions were gathered from the REgistro POliterapie Societa` Italiana di Medicina Interna (REPOSI) data for the years 2008, 2010 and 2012. 1,380 in-patients, 65+ years old, were enrolled in the first registry run, 1,332 in the second and 1,340 in the third. The prevalence of opioid prescription was calculated at hospital admission and discharge. In the third run of the registry, the degree of pain was assessed by means of a numerical scale. The prevalence of patients prescribed with opioids at admission was 3.8\ua0% in the first run, 3.6\ua0% in the second and 4.1\ua0% in the third, whereas at discharge rates were slightly higher (5.8, 5.3, and 6.6\ua0%). The most frequently prescribed agents were mild opioids such as codeine and tramadol. The number of total prescribed drugs was positively associated with opioid prescription in the three runs; in the third, dementia and a better functional status were inversely associated with opioid prescription. Finally, as many as 58\ua0% of patients with significant pain at discharge were prescribed no analgesic at all. The conservative attitude of Italian physicians to prescribe opioids in elderly patients changed very little between hospital admission and discharge through a period of 5\ua0years. Reasons for such a low opioid prescription should be sought in physicians\u2019 and patients\u2019 concerns and prejudices

Risk factors for hospital readmission of elderly patients.

BACKGROUND: The aim of this study was to identify which factors were associated with a risk of hospital readmission within 3 months after discharge of a sample of elderly patients admitted to internal medicine and geriatric wards. METHODS: Of the 1178 patients aged 65 years or more and discharged from one of the 66 wards of the 'Registry Politerapie SIMI (REPOSI)' during 2010, 766 were followed up by phone interview 3 months after discharge and were included in this analysis. Univariate and multivariate logistic regression models were used to evaluate the association of several variables with rehospitalization within 3 months from discharge. RESULTS: Nineteen percent of patients were readmitted at least once within 3 months after discharge. By univariate analysis in-hospital clinical adverse events (AEs), a previous hospital admission, number of diagnoses and drugs, comorbidity and severity index (according to Cumulative Illness Rating Scale-CIRS), vascular and liver diseases with a level of impairment at discharge of 3 or more at CIRS were significantly associated with risk of readmission. Multivariate logistic regression analysis showed that only AEs during hospitalization, previous hospital admission, and vascular and liver diseases were significantly associated with the likelihood of readmission. CONCLUSIONS: The results demonstrate the need for increased medical attention towards elderly patients discharged from hospital with characteristics such as AEs during the hospitalization, previous admission, vascular and liver diseases